Tag: covid vaccine

Long Covid: where we stand and challenges ahead

Abstract:

Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially as Long Covid, has been defined as a constellation of signs and symptoms which persist for weeks or months after the initial SARS-CoV-2 infection. PASC affects a wide range of diverse organs and systems, with manifestations involving lungs, brain, the cardiovascular system and other organs such as kidney and the neuromuscular system. The pathogenesis of PASC is complex and multifactorial. Evidence suggests that seeding and persistence of SARS-CoV-2 in different organs, reactivation, and response to unrelated viruses such as EBV, autoimmunity, and uncontrolled inflammation are major drivers of PASC. The relative importance of pathogenetic pathways may differ in different tissue and organ contexts. Evidence suggests that vaccination, in addition to protecting against disease, reduces PASC after breakthrough infection although its actual impact remains to be defined. PASC represents a formidable challenge for health care systems and dissecting pathogenetic mechanisms may pave the way to targeted preventive and therapeutic approaches.

Source: Mantovani, A., Morrone, M.C., Patrono, C. et al. Long Covid: where we stand and challenges ahead. Cell Death Differ (2022). https://doi.org/10.1038/s41418-022-01052-6 https://www.nature.com/articles/s41418-022-01052-6 (Full text)

Differences in Long-COVID Symptoms between Vaccinated and Non-Vaccinated (BNT162b2 Vaccine) Hospitalized COVID-19 Survivors Infected with the Delta Variant

Abstract:

This study compared differences in the presence of post-COVID symptoms among vaccinated and non-vaccinated COVID-19 survivors requiring hospitalization due to the Delta (B.1.617.2) variant. This cohort study included hospitalized subjects who had survived SARS-CoV-2 infection (Delta variant) from July to August 2021 in an urban hospital in Madrid, Spain. Individuals were classified as vaccinated if they received full administration (i.e., two doses) of BNT162b2 (“Pfizer-BioNTech”) vaccines. Other vaccines were excluded. Those with just one dose of the BNT162b2 vaccine were considered as non-vaccinated.
Patients were scheduled for a telephone interview at a follow-up around six months after infection for assessing the presence of post-COVID symptoms with particular attention to those symptoms starting after acute infection and hospitalization. Anxiety/depressive levels and sleep quality were likely assessed. Hospitalization and clinical data were collected from medical records. A total comprising 109 vaccinated and 92 non-vaccinated COVID-19 survivors was included.
Vaccinated patients were older and presented a higher number of medical comorbidities, particular cardiorespiratory conditions, than non-vaccinated patients. No differences in COVID-19 onset symptoms at hospitalization and post-COVID symptoms six months after hospital discharge were found between vaccinated and non-vaccinated groups. No specific risk factor for any post-COVID symptom was identified in either group.
This study observed that COVID-19 onset-associated symptoms and post-COVID symptoms six-months after hospitalization were similar between previously hospitalized COVID-19 survivors vaccinated and those non-vaccinated. Current data can be applied to the Delta variant and those vaccinated with BNT162b2 (Pfizer-BioNTech) vaccine.
Source: Fernández-de-las-Peñas C, Ortega-Santiago R, Fuensalida-Novo S, Martín-Guerrero JD, Pellicer-Valero OJ, Torres-Macho J. Differences in Long-COVID Symptoms between Vaccinated and Non-Vaccinated (BNT162b2 Vaccine) Hospitalized COVID-19 Survivors Infected with the Delta Variant. Vaccines. 2022; 10(9):1481. https://doi.org/10.3390/vaccines10091481 https://www.mdpi.com/2076-393X/10/9/1481/htm (Full text)

Risk of Long Covid in people infected with SARS-CoV-2 after two doses of a COVID-19 vaccine: community-based, matched cohort study

Abstract:

We investigated Long Covid incidence by vaccination status in a random sample of UK adults from April 2020 to November 2021. Persistent symptoms were reported by 9.5% of 3,090 breakthrough SARS-CoV-2 infections and 14.6% of unvaccinated controls (adjusted odds ratio 0.59, 95% CI: 0.50-0.69), emphasising the need for public health initiatives to increase population-level vaccine uptake.

Source: Daniel Ayoubkhani, Matthew L Bosworth, Sasha King, Koen B Pouwels, Myer Glickman, Vahé Nafilyan, Francesco Zaccardi, Kamlesh Khunti, Nisreen A Alwan, A Sarah Walker, Risk of Long Covid in people infected with SARS-CoV-2 after two doses of a COVID-19 vaccine: community-based, matched cohort study, Open Forum Infectious Diseases, 2022;, ofac464, https://doi.org/10.1093/ofid/ofac464 (Full text available as PDF file)

Predicting the efficacy of variant-modified COVID-19 vaccine boosters

Abstract:

As a result of the emergence and circulation of antigenically distinct SARS-CoV-2 variants, a number of variant-modified COVID-19 vaccines have been developed. Here we perform a meta-analysis of the available data on neutralisation titres from clinical studies comparing booster vaccination with either the current ancestral-based vaccines or variant-modified vaccines. We then use this to predict the relative efficacies of these booster vaccines under different scenarios.

Source: David S Khoury, Steffen S Docken, Kanta Subbarao, Stephen Kent, Miles Philip Davenport, Deborah Cromer. Predicting the efficacy of variant-modified COVID-19 vaccine boosters. medRxiv 2022.08.25.22279237; doi: https://doi.org/10.1101/2022.08.25.22279237 (Full article available as PDF file)

The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study

Abstract:

Background: Symptoms of post-acute sequelae of COVID-19 (PASC) may improve following SARS-CoV-2 vaccination. However few prospective data that also explore the underlying biological mechanism are available. We assessed the effect of vaccination on symptomatology of participants with PASC, and compared antibody dynamics between those with and without PASC.

Methods: RECoVERED is a prospective cohort study of adult patients with mild to critical COVID-19, enrolled from illness onset. Among participants with PASC, vaccinated participants were exact-matched 1:1 on age, sex, obesity status and time since illness onset to unvaccinated participants. Between matched pairs, we compared the monthly mean numbers of symptoms over a 3-month follow-up period, and, using exact logistic regression, the proportion of participants who fully recovered from PASC. Finally, we assessed the association between PACS status and rate of decay of spike- and RBD-binding IgG titers up to 9 months after illness onset using Bayesian hierarchical linear regression.

Findings: Of 349 enrolled participants, 316 (90.5%) had ≥3 months of follow-up, of whom 186 (58.9%) developed PASC. Among 36 matched pairs with PASC, the mean number of symptoms reported each month during 3 months of follow-up were comparable between vaccinated and unvaccinated groups. Odds of full recovery from PASC also did not differ between matched pairs (OR 1.57 [95%CI 0.46-5.84]) within 3 months after the matched time-point. The median half-life of spike- and RBD-binding IgG levels were, in days (95%CrI), 233 (183-324) and 181 (147-230) among participants with PASC, and 170 (125-252) and 144 (113-196) among those without PASC, respectively.

Interpretation: Our study found no strong evidence to suggest that vaccination improves symptoms of PASC. This was corroborated by comparable spike- and RBD-binding IgG waning trajectories between those with and without PASC, refuting any immunological basis for a therapeutic effect of vaccination on PASC.

Source: Wynberg E, Han AX, Boyd A, van Willigen HDG, Verveen A, Lebbink R, van der Straten K, Kootstra N, van Gils MJ, Russell C, Leenstra T, de Jong MD, de Bree GJ, Prins M; RECoVERED Study Group. The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study. Vaccine. 2022 Jun 7:S0264-410X(22)00748-4. doi: 10.1016/j.vaccine.2022.05.090. Epub ahead of print. PMID: 35725782; PMCID: PMC9170535. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170535/ (Full text)

Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2

The omicron variant of SARS-CoV-2 (PANGO B.1.1.529) spread rapidly across the world, out-competing former variants soon after it was first detected in November, 2021. According to the Our World in Data COVID-19 database, In Europe, the number of confirmed cases reported between December, 2021, and March, 2022 (omicron period) has exceeded all previously reported cases. Omicron appears to cause less severe acute illness than previous variants, at least in vaccinated populations. However, the potential for large numbers of people to experience long-term symptoms is a major concern, and health and workforce planners need information urgently to appropriately scale resource allocation.
In this case-control observational study, we set out to identify the relative odds of long-COVID (defined following the National Institute for Health and Care Excellence guidelines as having new or ongoing symptoms 4 weeks or more after the start of acute COVID-19) in the UK during the omicron period compared with the delta period. We used self-reported data from the COVID Symptom Study app. (King’s College London Research Ethics Management Application System number 18210, reference LRS-19/20-18210). Data were extracted and pre-processed using ExeTera13 (version 0.5.5).
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Source: Antonelli M, Pujol JC, Spector TD, Ourselin S, Steves CJ. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet. 2022 Jun 18;399(10343):2263-2264. doi: 10.1016/S0140-6736(22)00941-2. PMID: 35717982; PMCID: PMC9212672. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00941-2/fulltext (Full text)

High Prevalence of Both Previous Infection with SARS-CoV-2 and Persistent Symptoms

Abstract:

Introduction: Universities are unique settings with large populations, congregate housing, and frequent attendance of events in large groups. However, the current prevalence of previous COVID-19 infection in university students, including symptomatic and asymptomatic disease, is unknown. Our goal therefore was to determine the prevalence of previous infection, risk factors for infection, and the prevalence of persistent symptoms following infection among university students.

Methods: This was a cross-sectional study set in a large public university between January 22 and March 22, 2021. We surveyed students about demographics, risk factors, and symptoms, and simultaneously tested their saliva for IgA antibodies to SARS-CoV-2. To estimate the prevalence of previous infection we adjusted our intentional sample of a diverse student population for year in school and age to resemble the composition of the entire student body and adjusted for the imperfect sensitivity and specificity of the antibody test. Univariate and multiple regression analysis was used to identify independent risk factors for infection, and the proportion of students with persistent symptoms following acute infection was determined.

Results: A total of 488 students completed the survey, 432 had a valid antibody result, and 428 had both. The estimated prevalence of previous infection for 432 participants with valid antibody results was 41%. Of 145 students in our sample with a positive antibody test, 41.4% denied having a previous positive polymerase chain reaction (PCR) test for SARS-CoV-2 and presumably had an asymptomatic infection; in our adjusted analysis we estimate that approximately 2-thirds of students had asymptomatic infections. Independent risk factors for infection included male sex, having a roommate with a known symptomatic infection, and having two or fewer roommates. More frequent attendance of parties and bars was a univariate risk factor, but not in the multiple regression analysis. Of 122 students reporting a previous symptomatic infection, 14 (11.4%) reported persistent symptoms consistent with postacute COVID-19 a median of 132 days later.

Conclusions and relevance: Previous COVID-19 infection, both symptomatic and asymptomatic, was common at a large university. Measures that could prevent resurgence of the infection when students return to campus include mandatory vaccination policies, mass surveillance testing, and testing of sewage for antigen to SARS-CoV-2.

Source: Ebell MH, Forgacs D, Shen Y, Ross TM, Hulme C, Bentivegna M, Hanley HB, Jefferson AM, Hainess L. High Prevalence of Both Previous Infection with SARS-CoV-2 and Persistent Symptoms. J Am Board Fam Med. 2022 May-Jun;35(3):570-578. doi: 10.3122/jabfm.2022.03.210348. PMID: 35641057. https://www.jabfm.org/content/35/3/570 (Full text)

Long COVID after breakthrough SARS-CoV-2 infection

Abstract:

The post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—also referred to as Long COVID—have been described, but whether breakthrough SARS-CoV-2 infection (BTI) in vaccinated people results in post-acute sequelae is not clear.

In this study, we used the US Department of Veterans Affairs national healthcare databases to build a cohort of 33,940 individuals with BTI and several controls of people without evidence of SARS-CoV-2 infection, including contemporary (n = 4,983,491), historical (n = 5,785,273) and vaccinated (n = 2,566,369) controls. At 6 months after infection, we show that, beyond the first 30 days of illness, compared to contemporary controls, people with BTI exhibited a higher risk of death (hazard ratio (HR) = 1.75, 95% confidence interval (CI): 1.59, 1.93) and incident post-acute sequelae (HR = 1.50, 95% CI: 1.46, 1.54), including cardiovascular, coagulation and hematologic, gastrointestinal, kidney, mental health, metabolic, musculoskeletal and neurologic disorders.

The results were consistent in comparisons versus the historical and vaccinated controls. Compared to people with SARS-CoV-2 infection who were not previously vaccinated (n = 113,474), people with BTI exhibited lower risks of death (HR = 0.66, 95% CI: 0.58, 0.74) and incident post-acute sequelae (HR = 0.85, 95% CI: 0.82, 0.89). Altogether, the findings suggest that vaccination before infection confers only partial protection in the post-acute phase of the disease; hence, reliance on it as a sole mitigation strategy may not optimally reduce long-term health consequences of SARS-CoV-2 infection. The findings emphasize the need for continued optimization of strategies for primary prevention of BTI and will guide development of post-acute care pathways for people with BTI.

Source: Al-Aly, Z., Bowe, B. & Xie, Y. Long COVID after breakthrough SARS-CoV-2 infection. Nat Med (2022). https://doi.org/10.1038/s41591-022-01840-0  https://www.nature.com/articles/s41591-022-01840-0 (Full text)

Are vaccines a potential treatment for long covid?

Vaccines in the covid-19 pandemic have been a game changer in reducing rates of SARS-CoV-2 infection and hospital admission for, and death with, covid-19. They also reduce the chance of developing long covid by about half among people who are vaccinated before they develop covid-19.1 However, the effect of vaccines for people who already have long covid is a contentious area for both patients and healthcare professionals. In a linked paper, Ayoubkhani and colleagues (doi:10.1136/bmj-2021-069676) report findings from the largest published study on this topic to date.2 From a random sample of the UK population, they identified 28 356 adults (18-69 years) who were vaccinated after a positive SARS-CoV-2 test result, of whom 6729 (23.7%) reported long covid symptoms (>12 weeks) of any severity at least once during follow-up. Participants were followed for seven months to determine the relationship between vaccination, long covid, and symptom profiles after the first and second dose of either an adenovirus vector or mRNA vaccine.2

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Source: Manoj Sivan. Are vaccines a potential treatment for long covid? Cite this as: BMJ 2022;377:o988. https://www.bmj.com/content/377/bmj.o988.full (Full text)

Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study

Abstract:

Objective: To estimate associations between covid-19 vaccination and long covid symptoms in adults with SARS-CoV-2 infection before vaccination.

Design: Observational cohort study.

Setting: Community dwelling population, UK.

Participants: 28 356 participants in the Office for National Statistics COVID-19 Infection Survey aged 18-69 years who received at least one dose of an adenovirus vector or mRNA covid-19 vaccine after testing positive for SARS-CoV-2 infection.

Main outcome measure: Presence of long covid symptoms at least 12 weeks after infection over the follow-up period 3 February to 5 September 2021.

Results: Mean age of participants was 46 years, 55.6% (n=15 760) were women, and 88.7% (n=25 141) were of white ethnicity. Median follow-up was 141 days from first vaccination (among all participants) and 67 days from second vaccination (83.8% of participants). 6729 participants (23.7%) reported long covid symptoms of any severity at least once during follow-up. A first vaccine dose was associated with an initial 12.8% decrease (95% confidence interval -18.6% to -6.6%, P<0.001) in the odds of long covid, with subsequent data compatible with both increases and decreases in the trajectory (0.3% per week, 95% confidence interval -0.6% to 1.2% per week, P=0.51). A second dose was associated with an initial 8.8% decrease (95% confidence interval -14.1% to -3.1%, P=0.003) in the odds of long covid, with a subsequent decrease by 0.8% per week (-1.2% to -0.4% per week, P<0.001). Heterogeneity was not found in associations between vaccination and long covid by sociodemographic characteristics, health status, hospital admission with acute covid-19, vaccine type (adenovirus vector or mRNA), or duration from SARS-CoV-2 infection to vaccination.

Conclusions: The likelihood of long covid symptoms was observed to decrease after covid-19 vaccination and evidence suggested sustained improvement after a second dose, at least over the median follow-up of 67 days. Vaccination may contribute to a reduction in the population health burden of long covid, although longer follow-up is needed.

Source: Ayoubkhani D, Bermingham C, Pouwels KB, Glickman M, Nafilyan V, Zaccardi F, Khunti K, Alwan NA, Walker AS. Trajectory of long covid symptoms after covid-19 vaccination: community based cohort study. BMJ. 2022 May 18;377:e069676. doi: 10.1136/bmj-2021-069676. PMID: 35584816; PMCID: PMC9115603. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115603/ (Full text)